Comparison of threshold of toxicological concern (TTC) values to oral reference dose (RfD) values

Pham, Ly Ly; Borghoff, Susan J.; Thompson, Chad M.

doi:10.1016/j.yrtph.2020.104651

Cited by 10 publications

(4 citation statements)

References 25 publications

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“…In more detail, DIPTE values for PTEs showed the following order (mg/kg/day): Zn > Cu > Ni > Pb > Cr > U > V > Cd > Co > Sb, from the most to the less relevant element from a biological point of view. Moreover, when DIPTE values are compared with their respective reference dose (R fd ; Table 4), the consumption of AdV cloves resulted in an uptake of PTEs several orders of magnitude lower than the maximal oral reference dose which guarantees acceptable human exposure limits [43]. In addition, the HRI values of all the investigated PTEs (Table 4) were at least 100 times lower than the threshold of 1 (HRI << 1), indicative of no risk for human health as well as the complete improbability to develop carcinogenic effects [44].…”

Section: Resultsmentioning

confidence: 99%

Potentially Toxic Elements (PTEs) in Soils and Bulbs of Elephant Garlic (Allium ampeloprasum L.) Grown in Valdichiana, a Traditional Cultivation Area of Tuscany, Italy

et al. 2021

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The aim of this study was to provide, for the first time, data on the concentration of potentially toxic elements (PTEs) in soils and bulbs of elephant garlic (Allium ampeloprasum L.) cultivated in Valdichiana, a traditional agricultural area of Tuscany, Italy. Bulbs of elephant garlic and soil samples were collected in four cultivation fields and analyzed by inductively coupled plasma-mass spectrometry (ICP-MS) to determine the concentrations of As, Cd, Co, Cr, Cu, Ni, Pb, Sb, Tl, U, V, Zn. The concentrations of these PTEs in bulbs and cultivation soils were used to calculate geochemical, ecological and health risk indices. The results of this study suggest that, although bulbs of elephant garlic from the Valdichiana area may present slightly high concentrations of Cd, Ni and Pb, the associated health risk based on the daily intake is absolutely negligible. Cultivation soils had somewhat high Cu concentrations probably due to the diffuse use of Cu-based products in agriculture, but showed overall a very low ecological risk.

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Section: Resultsmentioning

confidence: 99%

Potentially Toxic Elements (PTEs) in Soils and Bulbs of Elephant Garlic (Allium ampeloprasum L.) Grown in Valdichiana, a Traditional Cultivation Area of Tuscany, Italy

et al. 2021

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“…For HFPO-DA, the TTC value is 433-fold higher than the RfD. As noted in Pham et al (2020) , a cursory examination of chemicals where the TTC value is significantly higher than corresponding RfD value indicated potential need for reevaluation of the RfD due to outdated methodology or overapplication/compounding of uncertainty factors. The fact that the RfD for HFPO-DA is significantly lower than the Cramer Class III TTC provides an additional line of evidence indicating that the RfD for HFPO-DA is overly conservative.…”

Section: Discussionmentioning

confidence: 98%

“…The expansion of the chemical space via the addition of PFAS resulted in a fifth percentile NOAEL value of 1.3 µg/kg-day (0.0013 mg/kg-day). An earlier evaluation demonstrated that, on average, Cramer Class III TTC values are ∼6-fold lower than corresponding IRIS values for the same chemical ( Pham et al , 2020 ), indicating that TTC values, which are generally used in data-poor situations, are more conservative than detailed risk assessment toxicity values (eg, RfDs). For HFPO-DA, the TTC value is 433-fold higher than the RfD.…”

Section: Discussionmentioning

confidence: 99%

Assessment of the mode of action underlying development of liver lesions in mice following oral exposure to HFPO-DA and relevance to humans

Heintz

Haws

Klaunig

et al. 2023

Toxicological Sciences

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HFPO-DA (ammonium, 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propanoate) is a short-chain polyfluorinated alkyl substance (PFAS) used in the manufacture of some types of fluorinated polymers. Like many PFAS, toxicity studies with HFPO-DA indicate the liver is the primary target of toxicity in rodents following oral exposure. Due to the structural diversity of PFAS, the mode of action (MOA) can differ between PFAS for the same target tissue. There is significant evidence for involvement of peroxisome proliferator-activated receptor alpha (PPARα) activation based on molecular and histopathological responses in the liver following HFPO-DA exposure, but other MOAs have also been hypothesized based on limited evidence. The MOA underlying the liver effects in mice exposed to HFPO-DA was assessed in the context of the Key Events (KEs) outlined in the MOA framework for PPARα activator-induced rodent hepatocarcinogenesis. The first three KEs (i.e., PPARα activation, alteration of cell growth pathways, and perturbation of cell growth/survival) are supported by several lines of evidence from both in vitro and in vivo data available for HFPO-DA. In contrast, alternate MOAs, including cytotoxicity, PPARγ and mitochondrial dysfunction are generally not supported by the scientific literature. HFPO-DA-mediated liver effects in mice are not expected in humans as only KE 1, PPARα activation, is shared across species. PPARα-mediated gene expression in humans produces only a subset (i.e., lipid modulating effects) of the responses observed in rodents. As such, the adverse effects observed in rodent livers should not be used as the basis of toxicity values for HFPO-DA for purposes of human health risk assessment.

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“…An exposure-driven risk assessment can be used to compare the expected exposure with the level of exposure that results in adverse effects as a basis of dictating whether further detailed experimental testing is needed. Early exposure-driven testing has made use of thresholds of toxicological concern (TTC) to prioritize the risk assessment of substances which require more data. This concept has been used for food, cosmetics, , and pharmaceuticals.…”

Section: Green Toxicology: the Principlesmentioning

confidence: 99%

Green Toxicology: Connecting Green Chemistry and Modern Toxicology

Krebs

McKeague

2020

Chem. Res. Toxicol.

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A major thrust in the concept of green chemistry is to eliminate the production of hazardous materials. Thus, sustainable toxicity testing is required for its successful implementation. Here, we present the principles of green toxicology, a concept less well known than green chemistry, but indispensable for the sustainable development of chemical products. Green toxicology entails early testing through non-animal methods, such as novel in vitro and in silico technologies in toxicity prediction, to obtain benign products in benign processes with reduced exposure. The future of non-testing toxicity prediction entails both an improved creation, management, and use of big data to optimize chemical space coverage and an increased mechanistic and biological pathway understanding which can be integrated in prediction tools. This perspective provides an introduction to chemists and toxicologists to the combined idea of green toxicology, rather than providing a comprehensive overview. Specifically, we (1) provide a brief overview of recently emerging technologies, (2) highlight the importance of collaboration between researchers to implement and integrate green toxicology in the chemical industry, and (3) present challenges that come along with the emerging technologies and propose possibilities for their better application and wider use in the future.

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Comparison of threshold of toxicological concern (TTC) values to oral reference dose (RfD) values

Cited by 10 publications

References 25 publications

Potentially Toxic Elements (PTEs) in Soils and Bulbs of Elephant Garlic (Allium ampeloprasum L.) Grown in Valdichiana, a Traditional Cultivation Area of Tuscany, Italy

Potentially Toxic Elements (PTEs) in Soils and Bulbs of Elephant Garlic (Allium ampeloprasum L.) Grown in Valdichiana, a Traditional Cultivation Area of Tuscany, Italy

Assessment of the mode of action underlying development of liver lesions in mice following oral exposure to HFPO-DA and relevance to humans

Green Toxicology: Connecting Green Chemistry and Modern Toxicology

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